HBeAg Positivity Research Articles

Development of strategies for screening, predicting, and diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers

This study aimed at developing strategies for screening, predicting, and diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers. A total of 1,360 infants born to 1,355 HBsAg positive mothers were followed for 1 year. All newborn infants received active and passive immunization within 24 hr after birth. Maternal and infant blood samples were collected and tested for the status of serum HBsAg, HBeAg, and HBV DNA positivity. The accuracy of infant HBsAg positivity, HBV DNA positivity, HBsAg and HBV DNA double positivity, and HBsAg and/or HBV DNA positivity at birth in the diagnosis of intrauterine HBV infection was evaluated by receiver operating characteristic curve analysis. Of 1,360 infants, 145 tested positive for HBsAg and/or HBV DNA at birth. Twenty-one (1.5%) infants, who were diagnosed with intrauterine HBV infection, showed HBsAg positivity from birth to 7 and 12 months of age. Infant HBsAg positivity at birth had the highest sensitivity in predicting intrauterine HBV infection, while neonatal HBsAg and HBV DNA double positivity had the highest specificity. These findings suggest that infants, who were born to HBsAg positive mothers and were positive for both HBsAg and HBV DNA at birth, may be at a higher risk for intrauterine HBV infection. HBsAg positivity at birth may be a good marker for screening intrauterine HBV infection. Infant HBsAg positivity both at birth and 7 months of age may be used as a diagnostic criterion to simplify diagnostic procedures and improve diagnostic efficiency.

Coinfection of hepatitis B and hepatitis delta virus in Belgium: A multicenter BASL study. Prospective epidemiology and comparison with HBV mono‐infection

Epidemiological data on hepatitis delta virus (HDV) infection in Belgium are lacking. A multicenter questionnaire-based registry on HDV infection was collated between March 1, 2008 and February 28, 2009. It consisted of patients coinfected with hepatitis B virus (HBV) and HDV. The data samples were compared to those of a concurrent registry on HBV infection. Prospective data of patients with HBV-HDV coinfection were collected. Active HBV replication is defined as HBeAg positivity or HBV DNA > 2,000 IU/ml. Forty-four patients from 15 centers were registered. A comparison of 29 patients infected with HDV (registered in the concurrent HBV registry) was made against 785 HBV mono-infected patients. The seroprevalence of patients coinfected with HBV and HDV in Belgium is reported to be 3.7% (29/785), consisting solely of the HBV-HDV coinfected patients in the HBV registry. This rises to 5.5% (44/800) if all patients infected with HDV from the two registries combined are included. The patients coinfected with HBV and HDV had higher (P < 0.05) ALT values and more advanced liver disease (Metavir score ≥F2), but had less active HBV replication and lower HBV DNA titers when compared with the patients infected only with HBV. Additionally, the majority of HBV-HDV coinfected patient was male, and 13.6% (6/44) of the patients that were coinfected HBV and HDV were also infected with HCV. In conclusion, this study provided much needed epidemiological data on the current state of HDV infection in Belgium.

Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia

In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non-HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme-linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non-HCC and 45 HCC patients infected with HBV/D, followed by age-matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti-HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non-HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age- and gender-adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8-118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3-17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3-84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high-risk patients and improving diagnostic and treatment strategies for HBV/D1.

To explore the safety testing evaluation index of breast-feeding by hepatitis B-positive mothers

To explore the safety testing evaluation index of breast-feeding by hepatitis B-positive mothers. HBV DNA from serum and breast milk of 252 hepatitis B-positive mothers were detected with the real-time quantitative PCR. The total positive rate of HBV DNA in serum had no difference with that in breast milk in hepatitis B-positive mothers (P > 0.05). The positive rate of HBV DNA in serum and breast milk of positive HBeAg were significantly higher than that of hepatitis B-positive mothers with negative HBeAg (P < 0.01). To detecte HBeAg and HBV DNA in serum and breast milk have important significance for guiding of breast feeding of hepatitis B-positive mothers.

Hepatotoxicity with chemotherapy in patients infected with hepatitis B virus.

9645 Background: Patients with chronic hepatitis B virus infection (HBV) are at risk for hepatotoxicity (HT) from viral reactivation during chemotherapy courses (TC). This can be minimized with antiviral prophylaxis (AV). Screening for HBV before TC remains controversial. Methods: A retrospective observational data only study was conducted at a Northern California integrated health care delivery system examining patients undergoing TC between 2000 and 2010. Patients were categorized as HBV positive (HBV+) if they had a positive HBsAg, HBeAg, or HBV DNA any time before and 1 year post TC. Grade 3 and 4 HT was determined using the National Cancer Institute Common Toxicity Criteria, with adaptation for those who had baseline abnormal liver function tests. We excluded patients with HIV, co-infection with both HBV and hepatitis C, and HBsAb of unclear provenance. Two control groups (CTRL1 and CTRL2) were established that had tested negative for HBV and HCV 1996 through 1 year after the last TC: CTRL1 tested negative for both before TC initiation (index TC); CTRL2 tested negative for one pre and the other post index TC or both at any time after index TC. AV prophylaxis (AVP+) was defined as anti-HBV medication given before HT; the remainder were AVP-, including those given AV after HT. Electronic medical record review was conducted on all HBV+ patients. Results: We identified 9,279 patients who received 15,960 TC; 57.8% were female with a mean age of 57.8 (±14.4) at TC initiation. 464 TC were given to 289 HBV+ patients; 22.8% had HT, with 7 deaths from HT, all AVP-. The rate of HT in the controls was 9.9% in CTRL1 (34/343), 12.6% in CTRL 2 (1907/15,153). Conclusions: These findings support the recommendation that all patients planning to receive TC should be screened for HBV. Those found positive should receive AV prophylaxis during therapy. [Table: see text]

Adiponectin and Its Receptors in Chronic Hepatitis B Patients With Steatosis in China

BackgroundHBV infection is a serious public health problem worldwide, which can contribute to the incidence of chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC).ObjectivesIn the present report, we assessed the association between adiponectin, its receptors and hepatic steatosis, fibrosis, and inflammation with hepatitis B virus.Patients and MethodsLiver biopsies from 89 patients with untreated chronic hepatitis B (34 steatosis vs. 55 without steatosis) were analyzed; liver biopsies from 50 healthy adults were used as control. The liver biopsies were subjected to routine histological examination, and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2).ResultsThe two groups were found to be comparable with respect to demographic, biochemical, metabolic, histological, and viral characteristics. BMI, γ-GT, FPG, insulin, and insulin sensitivity estimated by the HOMA index were significantly higher in patients with steatosis. The viral load of HBV and HBeAg positivity was higher in patients with steatosis than those without steatosis. High serum adiponectin levels were significantly correlated with abnormal serum ALT level (vs. normal ALT, P = 0.000), and HBV genotype C (vs. genotype B, P = 0.018). In patients with chronic HBV, the insulin sensitizing adipokine adiponectin, and its receptor AdipoR2were associated with steatosis. While adiponectin may becorrelated with inflammation, adiponectin, and its receptors were not associated with viral factors.ConclusionsOur results suggest that the role of adiponectin might be impaired in chronic hepatitis B with steatosis. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with steatosis. These findings indicated that reduced liver adiponectin expression may play an important role in the pathogenesis, and progression of CHB patients with steatosis. However, hepatic expression of adiponectin, and adipoR2 was not associated with various measures of HBV infection.

Familial clustering of HBV in families with children who are diagnosed as chronic hepatitis B or inactive carriers of HBV

The aim of this study was to assess and compare the spread of HBV infection in families with children who are diagnosed as chronic hepatitis B or are inactive carriers of HBV. A total of 570 patients aged 2-16 years and 2358 family members were included in the study. Patients were classified as inactive carriers (Group 1, 350 patients) or patients diagnosed as chronic active hepatitis B (Group 2, 220 patients). Demographic features of the families, HBV serological markers and routes of transmission were evaluated. Parental transmission was lower compared to nonparental transmission (34.8% and 65.1%, respectively). HBsAg positivity rate was found to be highest among mothers in both of the groups. HBeAg positivity and anti-HBs positivity were significantly higher in family members of Group 2. Transmission rates were significantly higher in families consisting of five or more members compared to families consisting of less than five members. HBsAg positivity of siblings was lowest when both parents were HbsAg negative and highest when both parents were HBsAg positive in both groups. A high risk of HBV transmission among mothers of HBsAg carriers and patients with chronic hepatitis B was demonstrated.

Demethylation pattern of PD-1 gene in promoter region is associated with the PD-1 expression on peripheral blood mononuclear cells in chronic hepatitis B patients

To observe the expression variations and influencing factors of programmed death one (PD-1) and DNA demethylation of PD-1 promoter on peripheral blood mononuclear cells (PBMCs) in chronic hepatitis B (CHB) patients and further investigate the relationship between the demethylation pattern of PD-1 gene in promoter region and the PD-1 expression on PBMC in CHB patients. A total of 162 subjects, including 144 CHB patients and 18 healthy blood donors, were enrolled. The expression of PD-1 on PBMCs was detected by flow cytometry. And the serum HBV markers, HBV DNA load and liver function were also measured. DNA of PBMCs was treated with sodium bisulfite; the PD-1 promoter fragments were amplified by polymerase chain reaction (PCR) and then transformed into Escherichia coli. Positive clones were selected for sequencing and the methylation status of fragments of PD-1 promoter was examined. With the PD-1 expression in normal controls (10.8% ± 4.4%) as a baseline level, the expression of PD-1 in CHB patients significantly increased. In CHB patients, the serum expression of PD-1 in PBMCs from patients with positive HBeAg (27.1% ± 18.4%) was much higher than that from those with negative HBeAg (19.6% ± 15.6%). And the expression level of PD-1 was not correlated with serum HBV DNA load and serum level of alanine aminotransferase. The results of bisulfite genomic sequencing showed that demethylation probability of some CG points in PD-1 promoter region (-601, -553, -538, -483, -463, -317 bp) were significantly correlated with PD-1 expression level (P < 0.05). The demethylation pattern of PD-1 gene in promoter region is associated with the PD-1 expression on PBMC in CHB patients.

Association between hepatitis B or hepatitis C virus infection and risk of pancreatic adenocarcinoma development: A systematic review and meta-analysis

BackgroundPancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus were detected in different extra-hepatic tissues, including pancreas. Objectivea systematic review and meta-analysis of epidemiological studies assessing PAC risk in patients with HBV/HCV chronic infections. MethodsIn September 2012, we extracted the articles published in Medline, Embase and the Cochrane Library, using the following search terms: “chronic HBV” and “HCV”, “hepatitis”, “PAC”, “risk factors”, “epidemiology”. Only case/control (C/C), prospective/retrospective cohort studies (PCS/RCS) written in English were collected. Resultsfour hospital-based C/C studies and one PCS, in HBV-infected patients and two hospital-based C/C studies and one RCS in HCV-infected subjects met inclusion criteria. In these studies HBsAg positivity enhanced significantly PAC risk (RR = 1.18, 95% CI:1.04–1.33), whereas HBeAg positivity (RR = 1.31, 95% CI:0.85–2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR = 1.12, 95% CI:0.78–1.59) and HBsAg negative/HBcAb positive/HBsAb negative pattern (RR = 1.30, 95% CI:0.93–1.84) did not. Relationship between PAC risk and anti-HCV positivity was not significant, although it reached a borderline value (RR = 1.160, 95% CI:0.99–1.3). ConclusionsHBV/HCV infection may represent a risk factor for PAC, but the small number of available researches, involving mainly populations of Asian ethnicity and the substantial variation between different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and genotypes are limiting factors to present meta-analysis.

Virological profile of hepatitis B infection in Black African HBsAg chronic carriers

Aims: 1) Describe virological profile of patients followed-up for chronic Hepatitis B virus (HBV); 2) Search for a correlation between cirrhosis and virological profile of patients. Patients and Methods: Retrospective study about 75 HBsAg positive patients followed-up for at least one year in two medical structures of Abidjan. Studied parameters: clinical signs, biological check-up (serum transaminases every 3 months for at least one year, platelets count and prothrombin rate), abdominal echography, virological check-up (HBsAg, HBeAg, anti-HBe, total anti-HBc, anti-VHC and anti- HIV Ab, HBV DNA biannual quantification during at least one year). Histological or biochemical evaluation of hepatic activity and fibrosis were realized in case of transaminases elevation or HBV DNA > 2000 IU/ml. Results: The mean age of our 75 patients (54 men) was 42.1 ± 11.54 years. HBV was fortuitously discovered in most of our patients (74.7% of the cases). The HBV inactive chronic carriage was 50.7%; HBeAg-positive and HBeAg-negative chronic hepatitis represented respectively 9.3% and 40% of the cases. Mean B viral load was 327.5 IU/ml in HBV inactive chronic carriers, 44,047,663 IU/ml in HBeAg-positive chronic HBV and 20,231,822 IU/ml in HBeAg-negative chronic HBV. Cirrhosis prevalence was significantly high- er in positive or negative HBeAg chronic HBV than in HBV inactive chronic carriers (32.4% vs. 5.3%, p = 0.008; OR = 8.6). Conclusion: Our patients’ virological profile was dominated by HBeAg-negative chronic HBV and HBV inactive chronic carriage. The risk of having cirrhosis was multiplied by 8.6 in case of active chronic hepatitis compared with HBV inactive chronic carriage.

Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positive Mothers

Perinatal HBV transmission is common in South East Asia approximately 25- 30% of the carrier pool. The problem is not only to the mother but also pertains to the offspring, in pregnancy hepatitis; the immune alterations in pregnancy may modify the dynamics of the disease. The infants of the mothers, who are carrying both HBsAg and HBeAg, have the highest risk of acquiring the HBV infection by the perinatal route. The over all risk may vary from one population to another, depending on the prevalence of HBeAg positivity in the pregnant women. It is reported and estimated that 22,000 pregnant women in the United States get infected with hepatitis B virus, which necessitated hepatitis B vaccination of the newborn mandatory in the United States.

Transfusion Transmitted Hepatitis B Virus among Multitransfused Thalassaemic Children in a Tertiary Health Care Centre in Bangladesh

Background: Repeated blood transfusion is the main life line support for thalassaemic children and so they are more prone to be infected with HBV. In Bangladesh the main source of blood for transfusion is the professional donors and so the possibility of HBV infection is higher. Objective: To assess the frequency of HBV among children who received more than 3 blood transfusions. Materials and Methods: This cross sectional analytical study was conducted in Pediatrics ward of Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of July 2003 to June 2004. Ninety five children aged less than 15 years, suffering from ? thalassaemia major and Hb E ? thalassaemia having blood transfusion more than three times and 20 controls of similar age and sex were included in this study. Seromarkers of HBV were tested and the results were analyzed using SPSS version Windows 11.0. Results: Out of 115 children 68 were ? thalassaemic (mean age 6.8 ± 2.84 yrs and male:female is 4.2:1), 27 were Hb E ? thalassaemic children (mean age 8.78 ± 2.99 yrs and M:F 1.4:1) and 20 were nontransfused, age and sex matched controls (mean age 6.23 ± 1.88 yrs and M:F 1:2.3). Out of 95 thalassaemic children 21 (22.1%) were positive for HBsAg. Among them 13 were ? thalassaemic and 8 were Hb E ? thalassaemic. None of the controls showed HBsAg positivity indicating a significant statistical difference (p=0.033). 28 (29.5%) children were positive for anti-HBc. Among them 23 were ? thalassaemic and 5 were Hb E ? thalassaemic and there was no core antigen positivity among the controls showing a significant statistical difference (p=0.022). Four (4.2%) patients showed HBeAg positivity, out of whom 3 were ? thalassaemic and 1 was Hb E ? thalassaemic. But this antigen was not found in any control and thereby, no statistical significant difference was observed (p=0.637). Among 20 controls, 2 were positive for anti-HBe antibody, but none of the thalassaemic children was positive for this antibody showing statistically significant difference (p=0.008). Conclusion: A significantly higher sero-prevalence of hepatitis B viral marker was observed among the multitransfused thalassaemic children. DOI: http://dx.doi.org/10.3329/jemc.v2i2.12838J Enam Med Col 2012; 2(2): 56-61

Should lamivudine monotherapy be stopped or continued in patients infected with hepatitis B with favorable responses after more than 5 years of treatment?

Regarding the limited evidence for determining the optimal duration of antiviral treatment for hepatitis B, the long-term outcome of patients with favorable responses to over 5 years of lamivudine monotherapy was investigated. Two hundred seventy-one patients who had received lamivudine for at least 5 years were enrolled. Ultimately, 72 patients without YMDD mutations and showing hepatitis B virus (HBV) DNA levels <2.5 pg/ml after 5 years of treatment were analyzed. Mean treatment duration with lamivudine was 9.1 ± 2.6 years. During the treatment, HBeAg and HBsAg loss/seroconversion rates were 95 and 6.9%, respectively. Decompensation and hepatocellular carcinoma (HCC) developed in 2.8 and 6.9% of patients, respectively. Old age and cirrhosis were risk factors for HCC development. Finally, 11.1% of patients developed YMDD mutations after 8.3 ± 2.4 years of treatment. There was no hepatic decompensation among the patients who developed delayed YMDD mutations. Sixteen patients who achieved a complete response stopped lamivudine and four patients showed relapses 10.3 ± 8.5 months after stopping lamivudine. Relapsed patients had more cirrhotic livers and higher rates of HBeAg positivity at 5 years than patients who maintained complete response. The present study suggests that patients who do not develop YMDD mutations over 5 years of treatment with lamivudine may continue lamivudine monotherapy until the loss of HBsAg. However, even for the patients showing favorable response over 5 years of treatment, those in older ages, with cirrhosis or who show poor HBeAg responses should be on careful monitoring to detect the development of viral mutations, relapse and even HCC.

Epidemiological, clinical and laboratory features of chronic hepatitis B infection in a cohort of immigrant and Italian patients from Ferrara, Italy

Background. Italy has recently become a land of immigration. Two hundred and fifty thousand carriers are immigrants and chronic HBV infection is the prevalent form. Considering the elevated number of foreigners resident in our province and the potential risk of transmission to local people, we retrospectively investigated the patterns of chronic hepatitis B (CHB) in 154 patients (76 foreigners, 78 Italians) observed in our Institution, with regard to demographic and clinical/laboratory characteristics.Results. The immigrants were younger (mean age 31 years) compared to Italians (51.5) and mainly came from East Europe. Regarding exposure to HBV, the intra-familial risk factor was most frequently observed in foreigners, compared to Italians (p = 0.03). Foreigners also showed a higher prevalence of HBeAg positive forms, HDV co-infection (7.9%) and abnormal ALT and/or HBV-DNA values, compared to Italians. HBeAg positivity was more associated with increased ALT (OR = 36.6, p = 0.001) than with elevated HBV viremia (OR = 6.5, p = 0.049); age was a protective factor (OR = 0.1; p = 0.014). No significant association was found between increased ALT and foreign nationality. The simultaneous presence of increased ALT and viremia was more frequent among foreigners, (OR = 7.6, p = 0,014) and increased with age (OR = 1.06, p = 0.013). Antiviral therapy was given in 7.8% of foreign citizens.Conclusion. Immigrants constitute a vulnerable population subgroup that would benefit from a more active approach regarding doctor-patient relationship for early recognition of HBV and treatment programmes.

Tenofovir Monotherapy and Tenofovir Plus Entecavir Combination as Rescue Therapy for Entecavir Partial Responders

Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients. We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir). All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir. Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.

Effect of fibronectin on HBV infection in primary human fetal hepatocytes in vitro

This study was carried out to investigate the effect of fibronectin (FN) on primary cultured human fetal hepatocytes infected by hepatitisB virus (HBV) invitro. Human fetal hepatocytes infected by HBV were cultured on culture dishes coated with FN invitro. HBsAg and HBeAg in supernatants were detected by ELISA, HBcAg in nuclei by immunohistochemistry, HBV DNA by fluorescent quantitative PCR and covalently closed circular DNA (cccDNA) by nested PCR. The results were compared with cells cultured on dishes that were not coated with FN. Positivity for HBsAg and HBeAg in supernatants appeared from day5 on the non-coated dishes, while positivity for HBsAg and HBeAg appeared from day1 on the coated dishes. Positivity for HBcAg in the nuclei on the non‑coated dishes was displayed from day2 with a positive rate of 15%, while positivity for HBcAg on the coated dishes was displayed from day1 with a positive rate of >90%. HBV DNA in cells on the non-coated dishes was detected from day4, while that on the coated dishes was detected from day1. The non-coated dishes were positive for cccDNA from day8, while the coated dishes were positive from day2. FN coating is capable of accelerating HBV infection in primary cultured fetal hepatocytes invitro, increasing the duration of HBV infection and the number of infected cells.

High HBV Viral Loads in HIV-Infected Pregnant Women at a Tertiary Hospital, South Africa

High HBV Viral Loads in HIV-Infected Pregnant Women at a Tertiary Hospital, South Africa

Clinical analysis of hepatitis B virus mutations related to adefovir dipivoxil among patients with chronic hepatitis B virus infection in eastern Zhejiang province

To explore the clinical characteristics of hepatic B virus (HBV) mutations related to adefovir dipivoxil (ADV) among patients with chronic HBV infection in eastern Zhejiang province and provide some reference values on normative usage of antiviral drugs. The data of chronic HBV-infected patients with HBV mutations related to ADV (n = 88) and non-mutation (n = 202) from June 2008 to August 2010 were analyzed retrospectively. The gene resistance mutations of HBV P region were analyzed by gene sequencing. And the HBV genotypes, HBV serum markers, HBV DNA levels and liver imaging findings were also analyzed. There were 9 cases with pre-existing mutations in 88 patients. The mutated sites were multiple and complicated. And the mutated sites related to other antiviral drugs were all accompanied by ADV-related mutations. The single mutated site was mostly at rtA181T (46.59%) and at rtV214A (11.36%). There were 27 cases (30.68%) with ≥ two mutated sites. The constituent ratios of males, end-stage liver diseases, complicated nonalcoholic fatty liver disease (NAFLD) and HBV genotype C infection in the mutation group were higher than those in the non-mutation group (P < 0.01, < 0.01, 0.019, 0.045). The average ages in the mutation group were also higher than those in the non-mutation group (P < 0.001). But the constituent ratios of HBeAg positivity and the levels of HBV DNA were lower (P = 0.002, 0.02). There may be some cases with pre-existing ADV-related mutations in ADV treatment-naive patients. The mutated sites occur at multiple loci, mostly at rtA181T and rtV214A. The male patients and those with a longer history of HBV infection, HBeAg negativity, HBV genotype C infection, illness progression and complicated NAFLD may be more susceptible to mutation. It is important for patients to accept and implement standardized regimens of antiviral drugs so as to prevent resistance and avoid salvage therapy.

HBeAg‐positive hepatitis delta: virological patterns and clinical long‐term outcome

The presence of the hepatitis B virus (HBV)-eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver-related clinical endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co-infected with the hepatitis D virus (HDV). We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti-HDV-positive patients. In addition, we compared the clinical long-term outcome of HBeAg-positive HDV-infected patients with HBeAg-negative control patients matched for age, gender and baseline-MELD score. HBeAg-positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co-infected patients. Sixty one per cent of the HBeAg-positive HDV-infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow-up. Both HBeAg-positive and -negative patients showed a similar severe clinical long-term course with about half of the patients developing a liver-related clinical complication after a median follow-up period of 51 months (range: 9-193 months). HBV DNA levels are low in both HBeAg-negative and HBeAg-positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long-term outcome of HBeAg-positive patients is not different to HBeAg-negative patients infected with the HDV.

Patterns of hepatitis B viral load level (HBV DNA), hepatitis B e antigen (HBeAg) status and risk factors of cirrhosis and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients in Thailand

Background: There is a strong relationship between HBeAg sero-status, HBV DNA level and CHB-associated complications, especially cirrhosis and HCC. However, the distribution of HBV DNA and HBeAg seroprevalence and risk factors of cirrhosis among Thai CHB patients have not been adequately described. We aim to determine the patterns of HBV DNA level, HBeAg status, and risk factors of cirrhosis and HCC in Thai CHB patients. Methods: A cross-sectional study was conducted at Chulabhorn Hospital in 2010. CHB patients, aged 20-65 years, were tested for liver function test , HBeAg, HBV DNA, alpha fetoprotein and ultrasound upper abdomen. Results: 2,293 CHB patients (1,086 (47.36%) males) with the mean age (SD) of 41.25 (10.95) years were included. Mean HBV DNA was 3.62(2.22) log 10 IU/ml, and 47.71% had HBV DNA > 2,000 IU/ml. HBeAg positivity was present in 17.2% and most cases (96.19%) had high HBV-VL > 2,000 IU/ml. The majority of CHB (82.8%) were HBeAg negative, and only 37.6% of them had HBV DNA > 2,000 IU/ml. ALT level was 35.5(40.1) IU/L, of which 22.5% had ALT > 40 IU/ml. Higher HBV DNA and increased ALT levels were significantly associated with male gender, HBeAg-seropositivity and cirrhosis (p< 0.001). Liver cirrhosis by liver biopsy, transient elastography and US was found in 180 (7.8%) cases. HBeAg-seropositivity was more frequently found in cirrhosis patients than HBeAg-seronegativity (23.33% vs 16.67%, p=0.023). High prevalence of cirrhosis was found in HBV DNA level 2-3 and 5-6 log 10 IU/ml in 18.33% and 18.89%, respectively (p<0.001). Multivariate analysis showed factors associated with cirrhosis, including male gender, age > 50 years and HBV DNA> 2000 IU/ml. Logistic regression analysis revealed HBV DNA level of 200,000-1,999,999 IU/ml, which significantly associated with cirrhosis (OR 5.84). Conclusion: Higher HBV DNA level, HBeAg-seropositivity and risk factors for cirrhosis were commonly found in Thai CHB patients. HBeAg negative with 39.34% viremic regardless of ALT were observed in most CHB cases. The predominant trend towards HBeAg –seronegativity CHB has also been observed as in western countries. Hence, the active national surveillance policy should be implemented in those with high HBV DNA and HBeAg-seropositivity to provide effective treatment and prevent complications.